Vitamin K Is Required For Synthesis Of Bloodclotting Proteins

Vitamin K was discovered as a result of investigations into the cause of a bleeding disorder—hemorrhagic (sweet clover) disease—of cattle, and of chickens fed on a fat-free diet. The missing factor in the diet of the chickens was vitamin K, while the cattle feed contained dicumarol, an antagonist of the vitamin. Antagonists of vitamin K are used to reduce blood coagulation in patients at risk of thrombosis—the most widely used agent is warfarin.

Three compounds have the biologic activity of vitamin K (Figure 45-7): phylloquinone, the normal dietary source, found in green vegetables; menaqui-nones, synthesized by intestinal bacteria, with differing lengths of side-chain; menadione, menadiol, and menadiol diacetate, synthetic compounds that can be metabolized to phylloquinone. Menaquinones are absorbed to some extent but it is not clear to what extent they are biologically active as it is possible to induce signs of vitamin K deficiency simply by feeding a phyl-loquinone deficient diet, without inhibiting intestinal bacterial action.

Free radical chain reaction

Superoxide PUFA — OH

Figure 45-6. Interaction and synergism between antioxidant systems operating in the lipid phase (membranes) of the cell and the aqueous phase (cytosol). (Rv free radical; PUFA-OOv peroxyl free radical of polyunsaturated fatty acid in membrane phospholipid; PUFA-OOH, hydroperoxy polyunsaturated fatty acid in membrane phospholipid released as hydroperoxy free fatty acid into cytosol by the action of phospholipase A2; PUFA-OH, hydroxy polyunsaturated fatty acid; TocOH, vitamin E (a-tocopherol); TocOv free radical of a-tocopherol; Se, selenium; GSH, reduced glutathione; GS-SG, oxidized glutathione, which is returned to the reduced state after reaction with NADPH catalyzed by glutathione reductase; PUFA-H, polyunsaturated fatty acid.)

Superoxide PUFA — OH

Figure 45-6. Interaction and synergism between antioxidant systems operating in the lipid phase (membranes) of the cell and the aqueous phase (cytosol). (Rv free radical; PUFA-OOv peroxyl free radical of polyunsaturated fatty acid in membrane phospholipid; PUFA-OOH, hydroperoxy polyunsaturated fatty acid in membrane phospholipid released as hydroperoxy free fatty acid into cytosol by the action of phospholipase A2; PUFA-OH, hydroxy polyunsaturated fatty acid; TocOH, vitamin E (a-tocopherol); TocOv free radical of a-tocopherol; Se, selenium; GSH, reduced glutathione; GS-SG, oxidized glutathione, which is returned to the reduced state after reaction with NADPH catalyzed by glutathione reductase; PUFA-H, polyunsaturated fatty acid.)

Vitamin K Is the Coenzyme for Carboxylation of Glutamate in the Postsynthetic Modification of Calcium-Binding Proteins

Vitamin K is the cofactor for the carboxylation of glutamate residues in the post-synthetic modification of proteins to form the unusual amino acid y-carboxygluta-mate (Gla), which chelates the calcium ion. Initially, vitamin K hydroquinone is oxidized to the epoxide (Figure 45-8), which activates a glutamate residue in the protein substrate to a carbanion, that reacts non-enzymically with carbon dioxide to form y-carboxyglut-amate. Vitamin K epoxide is reduced to the quinone by a warfarin-sensitive reductase, and the quinone is reduced to the active hydroquinone by either the same warfarin-sensitive reductase or a warfarin-insensitive quinone reductase. In the presence of warfarin, vitamin K epoxide cannot be reduced but accumulates, and is excreted. If enough vitamin K (a quinone) is provided in the diet, it can be reduced to the active hydroquinone by the warfarin-insensitive enzyme, and carboxylation can continue, with stoichiometric utilization of vitamin K and excretion of the epoxide. A high dose of vitamin K is the antidote to an overdose of warfarin.

Prothrombin and several other proteins of the blood clotting system (Factors VII, IX and X, and proteins C and S) each contain between four and six y-carboxygluta-mate residues which chelate calcium ions and so permit the binding of the blood clotting proteins to membranes. In vitamin K deficiency or in the presence of warfarin, an abnormal precursor of prothrombin (preprothrombin) containing little or no y-carboxyglutamate, and incapable of chelating calcium, is released into the circulation.

Phylloquinone

Phylloquinone

Menaquinone

Menaquinone

OH Menadiol

CH3 I 3 CO

CH3 I 3 CO

Menadiolo diacetate (acetomenaphthone)

Figure 45-7. The vitamin K vitamers. Menadiol (or menadione) and menadiol diacetate are synthetic compounds that are converted to menaquinone in the liver and have vitamin K activity.

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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